A vaccine against Marburg virus would be highly significant in preventing outbreaks which are both naturally occurring or the result of bioterrorist activity. To develop a safe and effective vaccine against the Marburg virus. Ebola and Marburg viruses have been identified as the cause of several highly lethal outbreaks of hemorrhagic fever for which there is no effective treatment or cure. Therefore, vaccine studies are critically important for protection against infection. We developed a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of primary immunization with plasmid DNA and boosting with adenoviral vectors containing Ebola genes generated protective immunity in cynomolgus macaques. The vaccine yielded 100% protective efficacy against Ebola infection and showed for the first time that protective immune responses could be generated in primates. The DNA vaccine is currently being tested in Phase I human clinical trials conducted by the VRC Clinical Trials Core Laboratory. In addition to our DNA prime/adenoviral vector boost vaccine studies, our laboratory has demonstrated that protective immunity to Ebola can be generated with a single inoculation of adenoviral vector vaccine 2, a result with significant implications for conducting enhanced ring vaccination during an Ebola outbreak. We have applied a similar strategy to the development of protective vaccines against Marburg virus.